The cAMP-Response Element Binding protein (CREB), and its extended family (CREM), is critically involved in adaptive responses to a wide variety of environmental signals. At the organismal level, this manifests itself in the large number of physiological responses (stress, circadian rhythms, memory formation, drug addiction and withdrawl) in which this protein family is involved. At the cellular level, a correspondingly bewildering number and combination of signal transduction pathways seem to ultimately converge upon these nuclear factors. We are interested in the molecular details of the involvement of dCREB2, the Drosophila homolog, in long-term memory formation. Previous work has clearly documented the important role that this gene plays in the process of fly memory formation. Currently, we are focused on a molecular description of signalling pathways which are activated during dCREB2-responsive transcription and memory formation, and how these affect the activity of the proteins which come from this gene. In addition, the mechanisms which are engaged during the switch from short-term to long-term memory are likely to impinge upon this gene, affecting the expression levels, activity and subcellular localization of various isoforms. Finally, we are interested in using CREB- responsive reporters to help visualize neurons which participate in Drosophila memory formation, and which might constitute part of the engram. The focus of our interest is the functional role of dCREB2 in these processes.